Side-stream volumetric capnography

ABSTRACT

Techniques for determining a volume of exhaled CO2 as a function of time using side-stream capnography, including obtaining flow dynamics measurements of a subject from a flow sensor; obtaining CO2 concentration measurements of the subject from a side-stream CO2 monitor; determining a duration of time (ΔTsl) for a sample of gas to flow from a reference point to the side-stream CO2 monitor; synchronizing in time the CO2 concentration measurement with the flow dynamics measurement, based on the determined ΔTsl; and determining a volume of CO2 exhaled as a function of time, based on the flow dynamics measurement and the synchronized CO2 concentration measurement.

CROSS-REFERENCE TO RELATED APPLICATION(S)

This application claims priority to U.S. Provisional Patent ApplicationNo. 62/336,663, filed on May 15, 2016, which is herein incorporated byreference in its entirety.

TECHNICAL FIELD

The present disclosure generally relates to the field of capnographyand, more specifically, to volumetric capnography using side-streamsampling.

BACKGROUND

This section is intended to introduce the reader to various aspects ofart that may be related to various aspects of the present invention,which are described and/or claimed below. This discussion is believed tobe helpful in providing the reader with background information tofacilitate a better understanding of the various aspects of the presentinvention. Accordingly, it should be understood that these statementsare to be read in this light, and not as admissions of prior art.

Carbon dioxide (CO₂) concentration can be plotted against time (timecapnogram) or expired volume (volumetric capnography). Volumetriccapnography involves the integration of flow or volume signals with CO₂concentration. That is, instantaneous CO₂ fractional concentration canbe plotted against the expired volume, thereby facilitating anassessment of CO₂ elimination, alveolar dead space, and rates ofemptying. Although volumetric capnography reveals importantphysiological information that cannot be obtained with time basedcapnography alone, the latter has become far more prevalent. This fortwo main reasons: a) time-based capnography is technically simpler,measuring only CO₂ concentrations; no integration of flow measurementsis needed; and b) volumetric capnography is realized to date only withintubated patients and, with that, limited to main-stream capnographydiscussed below.

Time based capnography, can be either diverting (i.e., side-stream) ornon-diverting (i.e., main-stream). In side-stream capnography airway gassamples are collected from the breathing circuit and the infrared sensoris located in a remote monitor. Breath samples are thus transported fromthe sampling site, through a sampling tube, to the sensor. However,side-stream systems are typically considered unable to providemeaningful comparisons between the flow and CO₂ waveforms because of thetime delay associated with such remote sampling.

Main-stream capnography uses an in-line CO₂ sensor connected directly tothe airway, and thus does not involve transport of breathing gases awayfrom the sampling site. Main-stream capnography provides measurement ofCO₂ concentrations directly from the patient airway (a few centimetersfrom the patient's mouth), when at this same point, an appropriatesensor is also placed to measure flow dynamics (generally using pressuredrop, or thermal change measurements over a short passage in theairway). Since both the flow dynamic and CO₂ concentration measurementsare practically instantaneous (when using non-dispersive IRspectroscopy), they are well synchronized and, hence, when calculatingabsolute CO₂ volume changes over exhalation time, a simplemultiplication of both parameters provides a fairly accurate result.However, main-stream capnography suffers from the limitation that it isspecifically defined for environments where there is a patient airway,i.e. for intubated patients, and is typically unsuitable fornon-intubated patients.

In side-stream capnography, on the other hand, gas samples are collectedfrom the breathing circuit, and the CO₂ sensor is located in a remotemonitor. Side-stream capnography is thus applicable for both intubatedpatients as well as non-intubated patients monitored using, for example,breath sampling cannulas. However, as mentioned above, inherent toside-stream capnograph there is a delay, e.g., a system response time,between the flow changes and the CO₂ calculation and display. That is,even though the ventilator provokes a fast change in flow direction(pressure) and dynamics, when changing between the inhalation andexhalation stages of the created breath, the actual monitored anddisplayed CO₂ waveforms are delayed with respect to these changes inflow direction. This delay is the result of ventilator dead spacevolumes, sampling delay, delay due to the measuring, processing anddisplaying of the CO₂ waveform, and time lags caused by thephysiological dead spaces. Such physiological deadspaces are generallynon-homogenous. Accordingly, the air volumes contained in thephysiological deadspaces change between patients having differentanatomical spaces and/or health conditions. Even for a given patient andset-up, the dead space volumes change depending on alveolar recruitmentand other physiological factors. Also, the transmit time of the sampledbreath from the sampling inlet to the measurement cell may be influencedby several factors, which may change between patient and over time.These factors include pump stability, accumulation of liquids in thesampling line and filter, sampling line tolerances etc.

SUMMARY

The above effects render side-stream capnograph data desynchronized fromflow dynamics measurements. Hence, side-stream capnography is typicallynot only a poor technological solution for providing volumetriccapnography, but one that is typically not applicable for volumetriccapnography. The present disclosure provides techniques to enablemonitoring and measuring of changes in flow dynamics and CO₂concentration measurements, while leveling out time delays related tothe CO₂ sampling system.

Advantageously, the techniques disclosed herein enable accurateside-stream volumetric capnography by calculating the time lag of theCO₂ concentration measurement, such that an accurate synchronization intime between flow dynamics and CO₂ concentrations is achieved. Thisadvantageously enables expanding volumetric capnography to non-intubatedpopulations.

Furthermore, the techniques disclosed herein enable volumetriccapnography when sampling is performed at the carina. In fact, samplingat the carina may further enhance the accuracy and/or sensitivity of thevolumetric capnography and its ability to provide insights into theventilation physiology, such as dead space breathing, shunt and EtCO₂ toPaCO₂ gradients, since performing the actual volumetric measurements atthe carina removes a major part of the anatomical dead space and airwaytubing dead space, leaving mainly those volumes that can change and thatare indicative of the patient's respiratory condition.

According to some embodiments, there is provided a method fordetermining a volume of exhaled CO₂ as a function of time usingside-stream capnography, the method including: obtaining flow dynamicsmeasurements of a subject from a flow sensor; obtaining CO₂concentration measurements of the subject from a side-stream CO₂monitor; determining a duration of time (ΔT_(sl)) for a sample of gas toflow from a reference point to the side-stream CO₂ monitor;synchronizing in time the CO₂ concentration measurement with the flowdynamics measurement, based on the determined ΔT_(sl); and determining avolume of CO₂ exhaled as a function of time, based on the flow dynamicsmeasurement and the synchronized CO₂ concentration measurement.

According to some embodiments, the determining of the ΔT_(sl) may beperformed based on an on-start of inhalation (T_(i)) a duration of timebetween T_(i) until the capnograph depicts a deflection in the CO₂concentration measurements (ΔT_(TOTAL)) and a time required to wash awaya gas volume encompassed between a Y-piece of a ventilator and the RP(ΔT_(FLUSH)).

According to some embodiments, the ΔT_(i) may be derived from the flowdynamics measurements.

According to some embodiments, the ΔT_(FLUSH) may be calculated based onthe inspiratory flow rate of the ventilator and the gas volumeencompassed between the Y-piece of the ventilator and the RP.

According to some embodiments, the ΔT_(sl) may be calculated based on adifference in ΔT_(TOTAL) obtained when supplying the volume of air at atleast two different flow rates.

According to some embodiments, the method may include providing a bolusof clean air or a bolus of air having known CO₂ concentration. Accordingto some embodiments, the bolus of clean air may be provided atinitiation of inhalation (T_(i)).

According to some embodiments, determining the ΔT_(sl) may includedetermining a time until a notch in the CO₂ concentration measurements,resulting from the bolus of clean air, is observed, and T_(i) maydetermined based on the flow dynamics measurements.

According to some embodiments, determining the ΔT_(sl) may includedetermining a time until a CO₂ concentration measurement, correspondingto the known concentration of the provided bolus, is observed, whereinthe known CO₂ concentration may include a concentration above a CO₂concentration possibly observed in exhaled breath.

According to some embodiments, the method may include determining anundistorted shape of a CO₂ waveform by applying a shape distortionfactor thereon. According to some embodiments, the CO₂ waveform may bederived from the CO₂ concentration measurements, and the shapedistortion factor may be calculated based on a shape of a notch in theCO₂ waveform resulting from the provided bolus of air.

According to some embodiments, the method may include displaying thevolume of CO₂ exhaled as a function of time on a display.

According to some embodiments, the method may be executed by a speciallyconstructed processing unit, such as a capnography monitor ormulti-purpose monitor, or it may be executed by a general purposecomputer specifically configured by a computer program stored in thecomputer.

According to some embodiments, there is provided a device configured todetermine a volume of exhaled CO₂ as a function of time, the deviceincluding: a side-stream CO₂ monitor configured to measure CO₂concentration over time; and a processor. According to some embodiments,the processor may be configured to: obtain flow dynamics measurements;obtain the CO₂ concentration measurements from the side-stream CO₂monitor; determine a duration of time (ΔT_(sl)) for a sample of gas toflow from a reference point to the side-stream CO₂ monitor; synchronizein time the CO₂ concentration measurement with the flow dynamicsmeasurement based on the determined ΔT_(sl); and determine a volume ofCO₂ exhaled as a function of time based on the flow dynamics measurementand the synchronized CO₂ concentration measurement.

According to some embodiments, the device may include a flow sensorconfigured to provide flow dynamics measurements.

According to some embodiments, the processor may be configured todetermine the ΔT_(sl) based on an inspiratory time (ΔT_(in)) and a timeto wash away a gas volume encompassed between a Y-piece of a ventilatorand the RP (ΔT_(FLUSH)).

According to some embodiments, the processor may be configured tocalculate the ΔT_(in) based on a volume of air supplied by theventilator and an inspiratory flow rate of the ventilator.

According to some embodiments, the processor may be configured tocalculate the ΔT_(FLUSH) based on the inspiratory flow rate of theventilator and the gas volume encompassed between the Y-piece of theventilator and the RP.

According to some embodiments, the processor may be configured tocalculate the ΔT_(FLUSH) based on a difference in ΔT_(in) obtained whensupplying the volume of air at at least two different flow rates.

According to some embodiments, the device may be configured to provide abolus of clean air or a bolus of air having a known CO₂ concentration.According to some embodiments, the device may include a tubing throughwhich the bolus of air having a known CO₂ concentration may be supplied.

According to some embodiments, the bolus of clean air may be provided atinitiation of inhalation (T_(i)). According to some embodiments, theprocessor may be configured to determine the ΔT_(sl) based on the bolusof clean air and based on a time until a notch in the CO₂ concentrationmeasurements, resulting from the bolus of clean air, is observed.According to some embodiments, the T_(i) may be determined based on theflow dynamics measurements.

According to some embodiments, the device may include a valve. Accordingto some embodiments, the processor may be configured to control theoperation of a valve. According to some embodiments, opening of thevalve provides the bolus of clean air.

According to some embodiments, controlling the operation of the valvemay include opening the valve such the said notch in the CO₂concentration measurements will occur during a plateau in the CO₂concentration measurements.

According to some embodiments, the processor may be configured todetermine the ΔT_(sl) based on the bolus of air having a known CO₂concentration and to determine a time until a CO₂ concentrationmeasurement, corresponding to the known concentration of the providedbolus, is observed. According to some embodiments, the known CO₂concentration may be a concentration above a CO₂ concentration possiblyobserved in exhaled breath.

According to some embodiments, the device may include a valve. Accordingto some embodiments, the processor may be further configured to controlthe operation of a valve. According to some embodiments, opening of thevalve may trigger the supply of the bolus of air having a known CO₂concentration.

According to some embodiments, the device may be configured to determinean undistorted shape of a CO₂ waveform by applying a shape distortionfactor thereon. According to some embodiments, the CO₂ waveform may bederived from the CO₂ concentration measurements, and the shapedistortion factor may be calculated based on a shape of a notch in theCO₂ waveform resulting from the provided bolus of air.

Certain embodiments of the present disclosure may include some, all, ornone of the above advantages. One or more technical advantages may bereadily apparent to those skilled in the art from the figures,descriptions and claims included herein. Moreover, while specificadvantages have been enumerated above, various embodiments may includeall, some or none of the enumerated advantages.

BRIEF DESCRIPTION OF THE DRAWINGS

Examples illustrative of embodiments are described below with referenceto figures attached hereto. In the figures, identical structures,elements or parts that appear in more than one figure are generallylabeled with a same numeral in all the figures in which they appear.Alternatively, elements or parts that appear in more than one figure maybe labeled with different numerals in the different figures in whichthey appear. Dimensions of components and features shown in the figuresare generally chosen for convenience and clarity of presentation and arenot necessarily shown in scale. The figures are listed below.

FIG. 1 shows an illustrative graph depicting time delays in CO₂concentration measurements;

FIG. 2 schematically illustrates a system configured to determine avolume of exhaled CO₂ as a function of time using side-streamcapnography, according to some embodiments;

FIG. 3 schematically illustrates a system configured to determine avolume of exhaled CO₂ as a function of time using side-streamcapnography, according to some embodiments;

FIG. 4 schematically illustrates a system configured to determine avolume of exhaled CO₂ as a function of time using side-streamcapnography, according to some embodiments;

FIG. 5 schematically illustrates a system configured to determine avolume of exhaled CO₂ as a function of time using side-streamcapnography, according to some embodiments;

FIG. 6 schematically illustrates a system configured to determine avolume of exhaled CO₂ as a function of time using side-streamcapnography, according to some embodiments;

FIG. 7 schematically illustrates a capnogram with a notch in CO₂concentration, according to some embodiments;

FIG. 8 is an illustrative flowchart of a method to perform volumetricside-stream capnograph, according to some embodiments;

FIG. 9 is an illustrative flowchart of a method to perform volumetricside-stream capnograph, according to some embodiments;

FIG. 10 is an illustrative flowchart of a method to perform volumetricside-stream capnograph, according to some embodiments;

FIG. 11 is an illustrative flowchart of a method to determine anundistorted shape of a CO₂ waveform, according to some embodiments; and

FIG. 12 is an illustrative flowchart of a method to perform volumetricside-stream capnograph, according to some embodiments.

DETAILED DESCRIPTION

In the following description, various aspects of the disclosure will bedescribed. For the purpose of explanation, specific configurations anddetails are set forth in order to provide a thorough understanding ofthe different aspects of the disclosure. However, it will also beapparent to one skilled in the art that the disclosure may be practicedwithout specific details being presented herein. Furthermore, well-knownfeatures may be omitted or simplified in order not to obscure thedisclosure. Additionally, it is to be explicitly understood that anycombination of any one or more of the disclosed embodiments may beapplicable and is within the scope of the disclosure.

Unless specifically stated otherwise, as apparent from the followingdiscussions, it is appreciated that throughout the specificationdiscussions utilizing terms such as “processing”, “computing”,“calculating”, “determining”, or the like, refer to the action and/orprocesses of an electronic processing system, such as a medical monitor,a computer or computing system, or similar electronic computing device,that manipulates and/or transforms data represented as physical, such aselectronic or electrical, quantities within the computing system'sregisters and/or memories into other data similarly represented asphysical quantities within the computing system's memories, registers orother such information storage, transmission or display devices.

Embodiments of the present techniques may include apparatus configuredto perform the operations herein. Such apparatus may be speciallyconstructed for the desired purposes, such as capnography monitors ormulti-purpose monitors, or it may include a general purpose computerselectively activated or reconfigured by a computer program stored inthe computer. Such a computer program may be stored in a computerreadable storage medium, such as, but is not limited to, any type ofdisk including floppy disks, optical disks, CD-ROMs, magnetic-opticaldisks, read-only memories (ROMs), random access memories (RAMs)electrically programmable read-only memories (EPROMs), electricallyerasable and programmable read only memories (EEPROMs), magnetic oroptical cards, or any other type of non-transitory memory media suitablefor storing electronic instructions, and capable of being coupled to acomputer system bus.

The processes and displays presented herein are not inherently relatedto any particular computer or other apparatus. Various general purposesystems may be used with programs in accordance with the teachingsherein, or it may prove convenient to construct a more specializedapparatus to perform the desired method. The desired structure for avariety of these systems will appear from the description below. Inaddition, embodiments of the present techniques are not described withreference to any particular programming language. It will be appreciatedthat a variety of programming languages may be used to implement theteachings of the inventions as described herein.

The present disclosure generally relates to systems, devices and methodsfor side-stream volumetric capnography, including synchronizing CO₂concentration measurements to breath flow dynamics measurements.

As used herein, the terms “patient” and “subject” may be interchangeablyused and may refer to any subject undergoing breath monitoring,specifically subjects monitored using side-stream capnography.

As used herein, the terms “breath inhalation initiation time” and“T_(i)” may be used interchangeably and may refer to the point in timewhen a flow of breath changes direction from exhalation to inhalation.As used herein the terms “breath exhalation initiation time” and “T_(e)”may be used interchangeably and may refer to the point in time when aflow of breath changes direction from inhalation to exhalation. Becauseof the inherent characteristics of gas flow dynamics and measurementtechniques, these points in time may be detected virtuallyinstantaneously along the entire patient airway.

As used herein, the terms “measurement delay” and “ΔT_(sl)” may refer tothe duration for any sample of gas to traverse (flow) from a referencepoint (RP—e.g. an airway adapter sampling input) to the capnograph. Asexplained herein, ΔT_(sl) may be of inter- and/or intra-patientvariability.

As used herein, the terms “reference point” and “RP” may refer to apoint in the patient airway at which a synchronized CO₂ concentration isdetermined. According to some embodiments, the RP may be an airwayadapter sampling input. According to some embodiments, the RP may bepositioned within a double lumen endotracheal tube.

As used herein, the terms “synchronized CO₂ measurements” and “CO₂-RP”may be used interchangeably and may refer to CO₂ values as a function oftime matched in time as if they were measured directly at the RP (devoidof sampling delay).

As used herein, the term “ΔT_(PDS)” (where PDS stands for physiologicaldead space) may refer to the time required to clean the physiologicaldead space from the previously inhaled clean air and to start seeing theCO₂ exhaled by the patient. That is, the term may refer to the delayfrom exhalation initiation (T_(e)—defined above) to an initial increasein CO₂-RP (as defined above) measurements, which is due to the patient'sphysiological dead space.

As used herein, the term “ΔT_(FLUSH)” may refer to the time to wash awaygases present in mechanical dead space (from the previous exhalation)i.e. the airway volume encompassed between the ventilator Y-piece andthe RP.

As used herein, the terms “inspiratory time” and “ΔT_(in)” may refer tothe time period during which a ventilator provides a volume of air to aventilated patient. The inspiratory time may be calculated from thevolume of air (V_(T)) provided to the patient and the inspiratory flowrate of the ventilator. As used herein, the terms “expiratory time” and“ΔT_(exp)” may refer to the time period during which a ventilatorremoves air from the ventilated patient.

As used herein, the terms “volume of exhaled CO₂” and “VCO₂” may referto the volume of CO₂ exhaled as a function of time, relative to the timepoints T_(i) and T_(e), and may be obtained by multiplying the flowdynamic signals and the time-matched CO_(2-RP) signals.

As used herein, the terms “physiological dead space” and “PDS” may beused interchangeably and refer to the volume of air, which is inhaledbut that does not take part in the gas exchange, because it remains inthe conducting airways (anatomical dead space), or because it reachesalveoli that are not perfused or poorly perfused (alveolar dead space).

As used herein, the term “anatomical dead space” is that portion of theairways (such as the mouth and trachea to the bronchioles) that conductsgas to the alveoli. No gas exchange is possible in these spaces. Thenormal value for dead space volume (in mL) averages about a third of theresting tidal volume (450-500 mL). According to some embodiments, theterms “physiological dead space” and “anatomical dead space” may be usedinterchangeably.

According to one aspect of the disclosure, there is provided a deviceand method for determining a volume of exhaled CO₂ as a function of timeusing side-stream capnography.

According to some embodiments, the method may include obtaining flowdynamics measurements of a subject from a flow sensor; obtaining CO₂concentration measurements of the subject from a side-stream CO₂monitor; determining a duration of time (ΔT_(sl)) required for a sampleof gas to flow from a reference point to the side-stream CO₂ monitor;synchronizing in time the CO₂ concentration measurement with the flowdynamics measurement, based on the determined ΔT_(sl); and determining avolume of exhaled CO₂ as a function of time, based on the flow dynamicsmeasurement and the synchronized CO₂ concentration measurement.

According to some embodiments, the ΔT_(sl) may be determined based onthe on-start of inhalation (Ti), which can be extracted from the flowmeasurements, and a time to wash away a gas volume (ΔT_(FLUSH))encompassed between a ventilator output (e.g. a ventilator Y-piece) andthe RP. According to some embodiments, the ΔT_(FLUSH) may be calculatedbased on the inspiratory flow rate of the ventilator and the gas volumeencompassed between the Y-piece of the ventilator and the RP or betweenthe endotracheal tube and the RP. The RP can also be moved closer to thepatient and even be positioned within the patient's trachea at thecarina. Thus, since the method obviates the need for placing the CO₂sensor at the sampling input, it advantageously enables volumetriccapnography in conjunction with endotracheal sampling using a doublelumen endotracheal tube.

This embodiment is based upon the different characteristics of theexhalation stage and the inhalation stage. Quantification of the timethat spans between the onset of exhalation (T_(e)) and the firstdetection of CO₂ at the RP, i.e. the calculation of ΔTsl, has somedifficulties. As mentioned hereinabove, on exhalation, the volume ofclean air that is removed from the physiological dead space, and theduration of this removal, is an unknown, which may depend upon manyparameters, changing between patients as well as changing during patientrespiratory fluctuations. The onset of the time delay resulting from thetransport of the sample from the sampling point to the monitor is thusunknown. The difficulty of assessing ΔTsl is further aggravated by thefact that not only is the CO₂ waveform delayed by a varying amount oftime, but it also has a gradual increase, which makes it difficult todefine and calculate the time between on-start of exhalation and CO₂concentration build up at the RP.

In the inhalation stage, on the other hand, the air volume (alsoreferred to as the mechanical dead space volume) encompassed between theventilator output (e.g., the ventilator Y-piece) and the RP, which isdriven back to the patient in order to refresh the patient with cleanair, is a quasi-fixed volume. This, because it is a purely mechanicalvolume, unrelated to the patient's complex physiology and body shape. Inaddition, initiation of inhalation is followed by an abrupt decrease inthe CO₂ concentration in the exhaled breath, manifested as a sharpdecline in the CO₂ waveform. As a result, defining and calculating thetime period between on-start of inhalation and a decrease in CO₂concentration at the RP is considerably simpler.

Since the on-start of inhalation (T_(i)) is obtainable from the flowmeasurements, the time between T_(i) until the capnograph depicts adeflection in the CO₂ concentration measurements (at the end of the CO₂waveform) is known. Consequently, ΔT_(sl) can be calculated, since thetotal delay (ΔT_(TOTAL)) equals the sum of ΔT_(FLUSH) and ΔT_(sl). TheΔT_(FLUSH) can be estimated from the deadspace volume (which is a fixedvolume) and the flow dynamics.

It is further understood, that even though the volume of the Y-piecesection is known and fixed, the actual time ΔT_(FLUSH) may not always beequal to multiplication of the flow rate and volume. This is because,during exhalation, there will usually be some exhaled breath that willdiffuse past the Y-junction into the ventilator side. In other words,not all the exhaled air will channel only into the other side of theY-junction used for removal. Hence, when inhalation starts, the wash outof the exhaled breath from the Y-piece to the sampling port of theairway will also include wash out of this diffused breath. However,since the level of diffused breath will be relative to the ventilatorparameters, a correction can be included as a function of flow rate tocorrect for these discrepancies. Additionally or alternatively, theY-piece can be designed such as to reduce to a minimum these affects,e.g. by adding a partial one-way valve at the Y-piece entrance to theventilator side. According to some embodiments, the method furtherincludes displaying the volume of exhaled CO₂ as a function of time, ona display.

According to another aspect of the disclosure, there is provided asystem, device and method for determining a volume of exhaled CO₂ as afunction of time using side-stream capnography. According to someembodiments, the method may include obtaining flow dynamics measurementsof a subject from a flow sensor; obtaining CO₂ concentrationmeasurements of the subject from a side-stream CO₂ monitor; determininga duration of time (ΔT_(sl)) for a sample of gas to flow from areference point to the side-stream CO₂ monitor; synchronizing in timethe CO₂ concentration measurement with the flow dynamics measurement,based on the determined ΔT_(sl); and determining a volume of exhaled CO₂as a function of time, based on the flow dynamics measurement and thesynchronized CO₂ concentration measurement.

According to some embodiments, determining of the ΔT_(sl) may beperformed based on an on-start of inhalation (T_(i)), and a duration oftime between T_(i) until the capnograph depicts a deflection in the CO₂concentration measurements (ΔT_(TOTAL)) (at the end of the CO₂waveform). According to some embodiments, the ΔT_(i) may be derived fromthe flow dynamics measurements. According to some embodiments, theΔT_(sl) may be calculated based on a difference in the total delay,ΔT_(TOTAL) obtained when supplying the volume of air at at least twodifferent flow rates.

This embodiment takes into consideration that additional elements may beincorporated into the sampling line (e.g. between the Y piece and thesampling port). This is, for example, the case where Heat and MoistureExchangers (HMEs) are used to create a humid and warm gas stream for thepatient. The HME may be placed between the sampling airway adapter andthe Y-piece, such that the large volume and filter of the HME does notinterfere with the breath sampling rise time. As a result, the airvolume (the mechanical deadspace volume) encompassed between the Y-pieceand the RP is unknown.

In order to overcome the issue of varying volumes in the patient airwaydesign, a technique disclosed herein suggests sampling air at twodifferent sampling rates with a calibrated sampling flow rate ratio “k”between them. As a non-limiting example, the first sampling flow ratemay be the conventional sampling flow rate of 50 ml/min, and the secondsampling flow rate may be 25 ml/min or 100 ml/min, e.g., with ratios “k”0.5 and 2 respectively.

Based on the different known sampling flow rates, the ΔT_(sl) may becalculated based on the below equations:ΔT1_(TOTAL) =ΔT _(flush) +ΔT _(sl), andΔT2_(TOTAL) =ΔT _(flush) +ΔT _(sl) ,*k

According to some embodiments, the two flow rates may be achieved byadding a two-way solenoid valve to the capnograph close to theabsorption cell where, in either or both paths, a different restrictoris incorporated. Hence, in the conventional mode, the restrictor ischosen to provide, for example, 50 ml/min, but when the solenoid isactivated, and the direction of flow changes and passes past the secondrestrictor, the flow is changed accordingly. Since it is only thedifference in restrictor that changes the flow rate, and both passiverestrictors are not anticipated to change over time (like pumps, orsampling lines or filters filling with liquids), a calibration, such asat the factory, can be made to measure accurately the ratio “k”, whichis then stored in the memory, where “k” may remain constant over thelife span even if the pump efficiency changes, since “k” is relative.According to some embodiments, the ratio “k” may change as a function ofambient temperature and pressure. Accordingly, according to someembodiments, the method may include adjusting “k” based on ambientpressure or temperature measurements. It is understood that theperiodical changes in the sampling flow rate would not disturbcontinuous operation of the capnograph since, at both flow rates, thecapnograph will retain its accuracy.

Advantageously, the method obviates the need for placing the CO₂ sensorat the sampling input and thus enables volumetric capnography inconjunction with endotracheal sampling using a double lumen endotrachealtube.

According to some embodiments, the method further includes displayingthe volume of exhaled CO₂ as a function of time on a display.

According to yet another aspect, there is provided a system, device andmethod for determining a volume of exhaled CO₂ as a function of timeusing side-stream capnography. According to some embodiments, the methodmay include obtaining flow dynamics measurements of a subject from aflow sensor; obtaining CO₂ concentration measurements of the subjectfrom a side-stream CO₂ monitor; determining a duration of time (ΔT_(sl))for a sample of gas to flow from a reference point to the side-streamCO₂ monitor; synchronizing in time the CO₂ concentration measurementwith the flow dynamics measurement, based on the determined ΔT_(sl); anddetermining a volume of exhaled CO₂ as a function of time, based on theflow dynamics measurement and the synchronized CO₂ concentrationmeasurement.

According to some embodiments, the ΔT_(sl) may be determined byproviding a bolus of clean air at initiation of inhalation (T_(i)) anddetermining a time required until a notch in the CO₂ concentrationmeasurements, resulting from the bolus of clean air, is observed.

As used herein, the term clean air may refer to ambient air or a gasused for oxygen supply. According to some embodiments, the clean air maybe substantially devoid of CO₂. According to some embodiments, the term“substantially devoid” may refer to a gas containing only residualand/or trace amounts of CO₂. According to some embodiments, the cleanair may have a CO₂ concentration of below 0.1%, below 0.05% or below0.04%. Each possibility is a separate embodiment. According to someembodiments, the clean air may be the gas supplied by the ventilator.

According to some embodiments, the T_(i) may be determined based on theflow dynamics measurements. This embodiment is designed to bypass theventilator airway paths and hence remove the flushing region out of theequation. Advantageously, this embodiment is thus also applicable fornon-intubated patients, for example subjects undergoing breathmonitoring using a breath sampling cannula. Advantageously, the methodalso enables volumetric capnography in conjunction with endotrachealsampling using a double lumen endotracheal tube.

According to some embodiments, the capnograph, the tubing connectedthereto and/or the ventilator may include an additional tube throughwhich the bolus of clean air is supplied. According to some embodiments,the additional tube may be connected on one side to a position close tothe sampling airway adapter inlet and on the other side to anappropriate position on the ventilator airway input section where thereis always clean air. According to some embodiments, the additional tubemay be configured to supply the clean air originating from theventilator to the sampling airway adaptor (the RP). According to someembodiments, the additional tube may be connected on one side close tothe inlet of a sampling tube and on the other side to a supply of cleanair.

According to some embodiments, a valve system may be incorporated intothe sampling system, such as on the side close to the sampling airwayadapter inlet. According to some embodiments, the valve may be normallyclosed, preventing clean air being pumped in. According to someembodiments, the valve may be closed when the capnograph is inmeasurement mode.

According to some embodiments, the valve may be opened for a shortperiod of time. According to some embodiments, the opening of the valvemay be coordinated with the flow dynamics measurements, such that theopening of the valve is triggered by a change in direction fromexhalation to inhalation. According to some embodiments, the operationof the valve and hence the injection of the bolus of clean air may bedefined using algorithms, which, based on learned characteristics aswell as measured patient respiration characteristics, enable triggeringthe injection at times so as to occur during the plateau of the CO₂waveform. According to some embodiments, the valve control mechanism mayinduce a plurality of injections at predefined time intervals, such thatat least one of the injections will occur when the CO₂ is at itsplateau, creating a noticeable notch whose timing can be measured fromthe signal trigger.

According to some embodiments, the operation of the valve may becontrolled by the capnograph. According to some embodiments, the openingof the valve may be controlled by the ventilator, such that theventilator change from exhalation to inhalation will trigger opening ofthe valve. According to some embodiments, the opening of the valve maybe controlled mechanically by the change in the flow pressure.

According to some embodiments, when the valve opens, a small bolus ofclean air may be injected into the sampling line input region.Consequently, the clean air dilutes the exhaled air then being sampled.This since, as mentioned above, even when the flow changes fromexhalation to inhalation, it is still the exhaled breath which is beingsampled, e.g., the CO₂ waveform will still be at its plateau. Accordingto some embodiments, the bolus of clean air then travels down thesampling line towards the capnograph, until reaching the sampling celland consequently being displayed on the capnograph monitor.

According to some embodiments, the bolus of clean air may besynchronized with the on start of inhalation (e.g. ventilatorinhalation), and the appearance of the sudden decrease (notch) in CO₂concentration may facilitate the measuring of ΔTsl. According to someembodiments, when the injection of the bolus is synchronized withinhalation start, its position will be slightly before the abrupt fallin CO₂, depictive of the start in inhalation and will be observed as anotch preceding the fall.

According to some embodiments, in order to ensure the accuracy of themeasurement, the position of the valve relative to the sampling line maybe of a same order of distance as the airway adapter sampling inlets tothe T-junction that connects the valve with the sampling line.

According to some embodiments, the valve may be configured to ensurethat the pressure drop created by the flow direction of the bolus ofclean air, when the valve is opened, is negligible, such that thecapnograph flow rate characteristics are prevented from beingsubstantially changed as a result thereof

According to some embodiments, the volume of the bolus of clean air maybe large enough to ensure that a recognizable notch in the CO₂concentration is created prior to the descent in CO₂ concentration(resulting from inhalation), while simultaneously ensuring that theaccuracy of the CO₂ concentration measurements is not compromised.According to some embodiments, the entry time of the bolus of clean airmay be long enough to ensure that a recognizable notch in the CO₂concentration is created prior to the descent in CO₂ concentration(resulting from inhalation), while simultaneously ensuring that theaccuracy of the CO₂ concentration measurements is not compromisedAccording to some embodiments, the entry time of the bolus of clean airmay be in the range of 50 msec-1 sec, 100 msec-600 msec or 200 msec-500msec, for example.

According to some embodiments, the valve may be a solenoid valve, acheck valve, a shut-off valve, a butterfly valve, a ball valve, adiaphragm, a pinch valve or any other suitable valve. Each possibilityis a separate embodiment. According to some embodiments, the valve maybe controlled electronically, by pressure or mechanically or any othersuitable control mechanism. Each possibility is a separate embodiment.According to some embodiments, the operation of the valve may becontrolled by the capnograph, by the ventilator, by an externalprocessor, manually or any combination thereof.

According to some embodiments, a signal may be received from thecapnograph, the ventilator, or an external processor recommendingmanually operation of the valve (e.g. open the valve). Additionally oralternatively, the valve may be manually operated according to a userprotocol. According to some embodiments, manually triggering (e.g.opening) the valve may induce a signal to the capnograph that the valvehas been opened, consequently triggering the measurement of the timedurations of travel. According to some embodiments, manual triggering ofthe valve may induce subsequent, optionally automatic, sequentialpulsatile openings of the valve so as to ensure timing with the plateauof the CO₂ concentration. According to some embodiments, the capnograph,the ventilator, or the external processor may be configured to calculatethe entry time of the bolus of clean air based on the opening of thevalve.

According to some embodiments, the ΔT_(sl) may be assessed periodicallyin order to improve accuracy. According to some embodiments, theperiodic assessment may be performed according to a predeterminedschedule. Alternatively, the ΔT_(sl) may be assessed based on identifiedchanges in the breathing pattern (e.g. changes in flow dynamic).

According to some embodiments, providing the bolus of clean air furtherenables to correct the spatial distribution of the obtained CO₂ waveform(representing the CO₂ concentration over time as calculated from the CO₂concentration measurements). When a gas samples flows through the sampletube, the part of the sample flowing closer to the walls of the samplingtube are slowed down due to the friction of the sampling tube's wall.The part of the sample flowing in the sampling tube's center thereforereaches the sampling cell prior to the part of the sample flowing alongthe sampling tube's wall. As a result, the waveform obtained when usingbreath sampling tubes as in side-stream capnography is spread outrelative to the waveform obtained when using an in-line CO₂ sensorconnected directly to the airway, as in main-stream capnography. Thedegree of spreading depends on the length of the sampling tube, on theincorporation of additional elements along the sampling line, such as,but not limited to, filters, and the like. By providing a bolus of cleanair, the distortion in the spatial distribution of the waveform can bemeasured and thus corrected for. This since the duration, and thus thevolume over time, of the bolus provided is known, and based upon thatthe anticipated shape of the notch can be determined. The deviationbetween the shape of the obtained notch and the anticipated shape cansubsequently serve as a transform and/or correction factor (alsoreferred to herein as a shape distortion factor), which can be appliedon the waveform obtained from the patient, so as to correct for thedistortion in its shape. According to some embodiments, the methodincludes displaying the volume of exhaled CO₂ as a function of time on adisplay and/or the undistorted CO₂ waveform on a display.

According to yet another aspect, there is provided a system, device andmethod for determining a volume of exhaled CO₂ as a function of timeusing side-stream capnography, the method including obtaining flowdynamics measurements of a subject from a flow sensor; obtaining CO₂concentration measurements of the subject from a side-stream CO₂monitor; determining a duration of time (ΔT_(sl)) for a sample of gas toflow from a reference point to the side-stream CO₂ monitor;synchronizing in time the CO₂ concentration measurement with the flowdynamics measurement, based on the determined ΔT_(sl); and determining avolume of exhaled CO₂ as a function of time, based on the flow dynamicsmeasurement and the synchronized CO₂ concentration measurements.

According to some embodiments, the ΔT_(sl) may be determined byproviding a bolus of air having a known CO₂ concentration anddetermining the time until a CO₂ concentration measurement,corresponding to the known concentration, is observed. According to someembodiments, the known CO₂ concentration may include a concentrationhigher than a CO₂ concentration potentially observed in exhaled breath.The abnormally high CO₂ concentration can then be identified as a peakin the CO₂ concentration measurements. According to some embodiments,the known CO₂ concentration may include a concentration lower than a CO₂concentration observed in exhaled breath. The abnormally low CO₂concentration can then be identified as a notch in the CO₂ concentrationmeasurements.

According to some embodiments, the T_(i) may be determined based on theflow dynamics measurements. As above, this embodiment is designed tobypass the ventilator airway paths and hence remove the flushing regionout of the equation. Advantageously, this embodiment is thus alsoapplicable for non-intubated patients, for example subjects undergoingbreath monitoring using a breath sampling cannula. Advantageously, themethod also enables volumetric capnography in conjunction withendotracheal sampling using a double lumen endotracheal tube.

According to some embodiments, the capnograph, the tubing connectedthereto and/or the ventilator may include an additional tube throughwhich the air having the known CO₂ concentration is supplied. Accordingto some embodiments, the additional tube may be connected on one side toa position close to the sampling airway adapter inlet and on the otherside to an appropriate gas supply. According to some embodiments, theadditional tube may be connected on one side close to the inlet of asampling tube and on the other side to a supply of air having the knownCO₂ concentration. According to some embodiments, the additional tubemay be configured to supply the air having the known CO₂ concentration,such as, but not limited to, room air, to the sampling airway adaptor(the RP).

As above, time for an injected bolus of gas to travel from the sampleline to the capnograph is utilized for calculating ΔT_(sl). However,according to this embodiment, the calculation is based on the knownconcentration of CO₂ in the injected gas. According to some embodiments,the air injected may be supplied from any gas source and may be injectedinto the sampling line, for example, by utilizing a valve.

According to some embodiments, the triggering of the valve may besynchronized in time with the onset of the inhalation. Alternatively,the triggering of the valve may not have to be synchronized in time withthe onset of the inhalation and may, for example, be provoked by thecapnograph periodically whenever it feels that new measurements arenecessary. As a non-limiting example, if the capnograph measures andmonitors its own flow rate, the capnograph may provoke a new measurementof ΔT_(sl) whenever the capnograph itself detects a change in its ownflow rate by more than a predefined level. This predefined level isbased upon a known accuracy level or resolution as required, or as suchone that would affect the final volumetric calculation.

According to some embodiments, the bolus of air having the known CO₂concentration may be synchronized with the on start of inhalation (e.g.ventilator inhalation), and the appearance of the sudden decrease orincrease (notch or peak) in CO₂ concentration may facilitate themeasuring of ΔT_(sl). According to some embodiments, when the injectionof the bolus is synchronized with inhalation start, its position will beslightly before the abrupt fall in CO₂, depictive of the start ininhalation and will be observed as a notch or a peak preceding the fall.

According to some embodiments, the operation of the valve and hence theinjection of the bolus of air having the known CO₂ concentration, may bedefined using algorithms, which, based on learned characteristics aswell as measured patient respiration characteristics, enable triggeringthe injection at times so as to occur during the plateau of the CO₂waveform. According to some embodiments, the valve control mechanism mayinduce a plurality of injections at predefined time intervals, such thatat least one of the injections will occur when the CO₂ is at itsplateau, creating a noticeable notch whose timing can be measured fromthe signal trigger.

According to some embodiments, the operation of the valve, and hence theinjection of the bolus of air having the known CO₂ concentration, mayoccur at any point of the breath cycle (i.e. at any point on the CO₂waveform).

According to some embodiments, the valve may be a solenoid valve, acheck valve, a shut-off valve, a butterfly valve, a ball valve, adiaphragm, a pinch valve or any other suitable valve. According to someembodiments, the valve may be controlled electronically, by pressure ormechanically or any other suitable control mechanism. According to someembodiments, the operation of the valve may be controlled by thecapnograph, by the ventilator, by an external processor, manually or anycombination thereof.

According to some embodiments, manual operation of the valve may be madebecause of a recommendation received from the capnograph, because of arecommendation received from ventilator, according to a user protocol orany combination thereof. According to some embodiments, manuallytriggering (e.g. opening) the valve may induce a signal to thecapnograph that the valve has been opened, consequently triggering themeasurement of the time durations of travel. According to someembodiments, manual triggering of the valve may induce subsequent,optionally automatic, sequential pulsatile openings of the valve so asto ensure timing with the plateau of the CO₂ concentration.

According to some embodiments, providing the bolus of clean air furtherenables to correct the spatial distribution of the obtained waveform(representing the CO₂ concentration over time as calculated from the CO₂concentration measurements). When a gas sample flows through the sampletube, the part of the sample flowing in the sampling tube's centerreaches the sampling cell prior to the part of the sample flowing alongthe sampling tube's wall, due to the friction caused by the wallmaterial. As a result, the waveform obtained when using breath samplingtubes as in side-stream capnography is distorted (spread out) relativeto the waveform obtained when using an in-line CO₂ sensor connecteddirectly to the patient airway, as in main-stream capnography. Thedegree of spreading depends on the length of the sampling tube, on theincorporation of additional elements along the sampling line, such as,but not limited to, filters and the like. By providing a bolus of cleanair, the distortion in the spatial distribution of the waveform can bemeasured and thus corrected for. This since the duration, and thus thevolume over time of the bolus provided, is known, and based upon thatthe anticipated shape of the notch can be determined. The deviationbetween the shape of the obtained notch and the anticipated shape cansubsequently serve as a transforming and/or correction factor (alsoreferred to herein as a shape distortion factor), which can be appliedon the waveform obtained from the patient, so as to correct for thedistortion in its shape.

According to yet another aspect of the disclosure there is provided amethod and device for determining an undistorted shape of a CO₂waveform. The method may include obtaining CO₂ concentrationmeasurements from a side-stream capnograph, deriving CO₂ waveformstherefrom and reefing the shape of the CO₂ waveforms by applying a shapedistortion factor thereon. According to some embodiments, the shapedistortion factor may be determined by providing a bolus of clean air(or air having a known CO₂ concentration, as essentially describedherein), determining the shape of a notch in the CO₂ waveform resultingfrom the provided bolus of gas and determining the deviation of thedetermined shape from that anticipated. That is, since the volume overtime of the provided bolus is known, the degree of distortion of itsflow through the sampling tube, caused by the friction exerted by thesampling tube's wall, may be determined.

Reference is now made to FIG. 1, which shows an illustrative graph 100depicting the time delays in CO₂ concentration measurements. After theonset of exhalation T_(e), there will be a first time lag, ΔT_(PDS),preceding the increase in CO₂ at the sampling site. This time lag is dueto the time required to promote cleaning of the physiological dead spacefrom previously inhaled air, which has remained in the conductingairways, and thus not taken part in the gas exchange. At T_(PDS) “real”exhalation, i.e. air that takes part in the gas exchange, is commenced.However, a second time lag, ΔT_(sl), is incurred to the time necessaryfor the gas sample to traverse (flow) from the reference point (RP) toit being sensed and calculated by the capnograph. The T_(e) willtherefore be measured only at T_(S), i.e. at a total time delay ofΔT_(PDS)+ΔT_(sl) and at a time delay of ΔT_(sl) from the actual increasein CO₂ in the exhaled breath. The measured CO₂ waveform is thus shifted(dotted line) relative to flow dynamics measurements.

Reference is now made to FIG. 2, which schematically illustrates asystem 200 for determining a volume of exhaled CO₂ as a function of timeusing side-stream capnography. System 200 includes a ventilator 250connected to a patient 201 through an airway adaptor 220. Exiting airwayadaptor 220 is a breath sampling tube 215 configured to allow breathsamples being drawn from airway adapter 220 for measurement byside-stream CO₂ monitor 210 (e.g. a capnograph). System 200 furtherincludes a processor 230 here depicted as an integral part ofside-stream CO₂ monitor 210, however other options, such as, forexample, an external processor, are also applicable and thus within thescope of the disclosure. Processor 230 is configured to obtaining flowdynamics measurements from a flow sensor 240 and CO₂ concentrationmeasurements form a CO₂ sensor 260 (e.g. a Nondispersive Infrared (NDIR)CO₂ Sensor). Flow sensor 240 may, as here depicted, be an integral partof side-stream CO₂ monitor 210, however other configurations, (e.g. aseparate flow sensor) are also applicable and as such within the scopeof the present disclosure. Processor 230 is further configured todetermine a duration of time (ΔT_(sl)) for a sample of gas to flow froma reference point 225 in airway adapter 220 to side-stream CO₂ monitor210, to synchronize in time the CO₂ concentration measurement with theflow dynamics measurement, based on the determined ΔT_(sl) and todetermine a volume of exhaled CO₂ as a function of time, based on theobtained flow dynamics measurement and the synchronized CO₂concentration measurement.

Processor 245 may determine the ΔT_(sl) based on the on-start ofinhalation (Ti), extracted from the flow measurements, and on a timerequired to wash away a gas volume (ΔT_(FLUSH)) encompassed betweenventilator Y-piece 230 and airway adaptor 220. Optionally, theΔT_(FLUSH) may be calculated based on the inspiratory flow rate of theventilator and the fixed gas volume encompassed between Y-piece 230 andairway adaptor 220.

It is understood, that even though the volume of Y-piece 230 is known,the actual time ΔT_(FLUSH) may not always be equal to multiplication ofthe flow rate and volume. Thus, because during exhalation there may besome exhaled breath diffusing past Y-piece 230 into a ventilator side235 of Y-piece 230, e.g., not all the exhaled air will channel into theexhaust side 237 of Y-piece 230 used for removal. Hence, when inhalationstarts, the wash out of the exhaled breath from Y-piece 230 to asampling inlet 217 of airway adapter 220 may also include wash out ofthis diffused breath. However, since the level of diffused breath willbe relative to the parameters of ventilator 250, a correction can beincluded as a function of flow rate to correct for these discrepancies.Additionally or alternatively, Y-piece 230 can be designed such as toreduce to a minimum these affects, e.g. Y-piece 230 may include apartial one-way valve at an entrance into ventilator side 235 of Y-piece230.

Reference is now made to FIG. 3, which schematically illustrates asystem 300 for determining a volume of exhaled CO₂ as a function of timeusing side-stream capnography. System 300 includes a ventilator 350,connected to a patient 301 through an airway adaptor 320, and a heat andmoisture exchanger 390 positioned between airway adapter 320 and aY-piece 330 of ventilator 350. Exiting airway adaptor 320 is a breathsampling tube 315 configured to allow breath samples being drawn fromairway adapter 320 for measurement by side-stream CO₂ monitor 310 (e.g.a capnograph). System 300 further includes a processor 345 here depictedas an integral part of side-stream CO₂ monitor 210, however otheroptions, such as for example an external processor is also applicableand thus within the scope of the disclosure. Processor 345 is configuredto obtain flow dynamics measurements from a flow sensor 340 and CO₂concentration measurements form a CO₂ sensor 360 (e.g. a NondispersiveInfrared (NDIR) CO₂ Sensor). Flow sensor 340 may, as here depicted, bean integral part of side-stream CO₂ monitor 310, however otherconfigurations, (e.g. a separate flow sensor) are also applicable and assuch within the scope of the present disclosure. Processor 345 isfurther configured to determine a duration of time (ΔT_(sl)) requiredfor a sample of gas to flow from a reference point 325 in airway adapter320 to side-stream CO₂ monitor 310, to synchronize in time the CO₂concentration measurement with the flow dynamics measurement, based onthe determined ΔT_(sl) and to determine a volume of exhaled CO₂ as afunction of time, based on the obtained flow dynamics measurement andthe synchronized CO₂ concentration measurement.

Processor 345 may determine the ΔT_(sl) based an on-start of inhalation(T_(i)), and a duration of time between T_(i) until side-stream CO₂monitor 310 depicts a deflection in the CO₂ concentration measurements(ΔT_(TOTAL)) (at the end of the CO₂ waveform). ΔT_(sl) may then becalculated by processor 345 based on a difference in the total delay,ΔT_(TOTAL), obtained when supplying the volume of air at at least twodifferent flow rates.

Due to the incorporation of heat and moisture exchangers 390, the airvolume (the mechanical dead space volume) encompassed between Y-piece330 and airway adapter 320 is unknown. However, based on the differentknown sampling flow rates, heat and moisture exchangers 390 may be takenout of the equation and ΔT_(sl) may be calculated, as described herein.

According to some embodiments, the different flow rates, may be achievedby adding a two-way solenoid valve 312 to side-stream CO₂ monitor 310close to the absorption cell (not shown), where in either or both paths,a restrictor (not shown) is incorporated, such that when two-waysolenoid valve 312 is activated, and the direction of flow changes andpasses past the restrictor, the flow is changed accordingly. Since it isonly the difference in the restrictor that changes the flow rate, andrestrictors are not anticipated to change over time (as opposed topumps, sampling lines or filters), a factory calibration can be made tomeasure accurately the ratio “k”, which can then be stored in processor345. The ratio “k” may change as function of ambient temperature andpressure. Processor 345 may therefore be configured to adjust “k” basedon ambient pressure or temperature measurements.

Reference is now made to FIG. 4, which schematically illustrates asystem 400 for determining a volume of exhaled CO₂ as a function of timeusing side-stream capnography. System 400 includes a ventilator 450connected to a patient 401 through an airway adaptor 420. Exiting airwayadaptor 420 is a breath sampling tube 415 configured to allow breathsamples being drawn from airway adapter 420 for measurement byside-stream CO₂ monitor 410 (e.g. a capnograph). System 400 furtherincludes a processor 445 here depicted as an integral part ofside-stream CO₂ monitor 410, however other options, such as, forexample, an external processor is also applicable and thus within thescope of the disclosure. Processor 445 is configured to obtain flowdynamics measurements from a flow sensor 440 and CO₂ concentrationmeasurements from a CO₂ sensor 460 (e.g. a Nondispersive Infrared (NDIR)CO₂ Sensor). Flow sensor 440 may, as here depicted, be an integral partof side-stream CO₂ monitor 410, however other configurations, (e.g. aseparate flow sensor) are also applicable and as such within the scopeof the present disclosure. Processor 445 is further configured todetermine a duration of time (ΔT_(sl)) for a sample of gas to flow froma reference point 425 in airway adapter 420 to side-stream CO₂ monitor410, to synchronize in time the CO₂ concentration measurement with theflow dynamics measurement, based on the determined ΔT_(sl) and todetermine a volume of exhaled CO₂ as a function of time, based on theobtained flow dynamics measurement and the synchronized CO₂concentration measurement.

Processor 445 may determine the ΔT_(sl) by providing a bolus of cleanair at initiation of inhalation (T_(i)) and determining a time requireduntil a notch in the CO₂ concentration measurements (and/or the CO₂waveform derived therefrom), resulting from the bolus of clean air, isobserved.

Processor 445 may further determine a shape distortion factor based onthe shape of the notch in the CO₂ waveform and its deviation from ananticipated shape, as described herein. The shape distortion factor maysubsequently be utilized by processor 445 to cancel out distortions tothe shape of the CO₂ waveform caused by friction of the sampling tube'swall on breath sample flow therein, thereby enabling the determining ofthe “true” shape of the obtained CO₂ waveform.

To provide the bolus of clean air, system 400 includes a tube 485through which the bolus of clean air is supplied. Tube 485 is connectedon one side to a position close to sampling inlet 417 of airway adapter420 and on the other side to ventilator 450. Tube 485 can thus supplythe clean air originating from the ventilator to inlet 417.

System 400 further includes a valve 487 positioned in proximity to inlet417. Valve 487 may be normally closed, preventing clean air from beingpumped in at all times. Valve 487 may be opened for a short period oftime and the opening may, for example, be coordinated with the flowdynamics measurements, such that the opening of the valve is triggeredby a change in direction from exhalation to inhalation. Additionally oralternatively, operation of valve 487 and hence the injection of thebolus of clean air, may be defined using algorithms, which, based onlearned characteristics as well as measured patient respirationcharacteristics, enable triggering the injection so as to occur duringthe plateau of the CO₂ waveform. Additionally or alternatively, valve487 may induce a plurality of injections at predefined time intervals,such that at least one of the injections will occur when the CO₂ is atits plateau, creating a noticeable notch whose timing can be measuredfrom the signal trigger. Processor 430 may then be configured todetermine ΔT_(sl) based on the time for the bolus of clean air to bemeasured by capnograph 410 and to create a notch in the CO₂ waveform, asdepicted in FIG. 7.

Reference is now made to FIG. 5, which schematically illustrates asystem 500 for determining a volume of exhaled CO₂ as a function of timeusing side-stream capnography. System 500 includes a ventilator 550connected to a patient 501 through an airway adaptor 520. Exiting airwayadaptor 520 is a breath sampling tube 515 configured to allow breathsamples being drawn from airway adapter 520 for measurement byside-stream CO₂ monitor 510 (e.g. a capnograph). System 500 furtherincludes a processor 545 here depicted as an integral part ofside-stream CO₂ monitor 510, however other options, such as, forexample, an external processor is also applicable and thus within thescope of the disclosure. Processor 545 is configured to obtaining flowdynamics measurements from a flow sensor 540 and CO₂ concentrationmeasurements form a CO₂ sensor 560 (e.g. a Nondispersive Infrared (NDIR)CO₂ Sensor). Flow sensor 540 may, as here depicted, be an integral partof side-stream CO₂ monitor 510, however other configurations, (e.g. aseparate flow sensor) are also applicable and as such within the scopeof the present disclosure. Processor 545 is further configured todetermine a duration of time (ΔT_(sl)) for a sample of gas to flow froma reference point 525 in airway adapter 520 to side-stream CO₂ monitor510, to synchronize in time the CO₂ concentration measurement with theflow dynamics measurement, based on the determined ΔT_(sl) and todetermine a volume of exhaled CO₂ as a function of time, based on theobtained flow dynamics measurement and the synchronized CO₂concentration measurement.

Processor 545 may determine the ΔT_(sl) by providing a bolus of airhaving a known CO₂ concentration and determining the time until a CO₂concentration measurement, corresponding to the known concentration, isobserved. The known CO₂ concentration may include a concentration higherthan a CO₂ concentration potentially observed in exhaled breath, thusleading to a peak in the CO₂ concentration measurement. Alternatively,the known CO₂ concentration may include a concentration lower than a CO₂concentration observed in exhaled breath, thus causing a notch in theCO₂ concentration measurement (and/or the CO₂ waveform derivedtherefrom).

Processor 545 may further determine a shape distortion factor based onthe shape of the notch in the CO₂ waveform and its deviation from ananticipated shape, as described herein. The shape distortion factor maysubsequently be utilized by processor 545 to cancel out distortions tothe shape of the CO₂ waveform caused by friction of the sampling tube'swall on breath sample flow therein, thereby enabling the determining ofthe “true” shape of the obtained CO₂ waveform.

To provide the bolus of clean air, system 500 includes a tube 585through which the bolus of clean air is supplied. Tube 585 is connectedon one side to a position close to sampling inlet 517 of airway adapter520 and on the other side to an air supply 589 configured to supply thebolus of air having the known CO₂ concentration.

System 500 further includes a valve 587 positioned in proximity to inlet517. Valve 587 may be normally closed, preventing clean air from beingpumped in at all times. Valve 587 may be opened for a short period oftime and the opening may, for example, be coordinated with the flowdynamics measurements, such that the opening of the valve is triggeredby a change in direction from exhalation to inhalation. Additionally oralternatively, operation of valve 587 and hence the injection of thebolus of air having the known CO₂ concentration may be defined usingalgorithms, which, based on learned characteristics as well as measuredpatient respiration characteristics, enable triggering the injection soas to occur during the plateau of the CO₂ waveform. Additionally oralternatively, valve 587 may induce a plurality of injections ensuringthat the notch/peak is identifiable. Processor 545 may then beconfigured to determine ΔT_(sl) based on the time for the bolus of cleanair to be measured by capnograph 510 and to create a notch in the CO₂waveform, as depicted in FIG. 7.

Reference is now made to FIG. 6, which schematically illustrates asystem 600 for determining a volume of exhaled CO₂ as a function of timeusing side-stream capnography. System 600 includes a gas samplingcannula 650 connected to a patient 601 and allowing breath samples toflow through sampling tube 615 for measurement by side-stream CO₂monitor 610 (e.g. a capnograph). System 600 further includes a processor645 here depicted as an integral part of side-stream CO₂ monitor 610,however other options, such as, for example, an external processor isalso applicable and thus within the scope of the disclosure. Processor645 is configured to obtaining flow dynamics measurements from a flowsensor 640 and CO₂ concentration measurements form a CO₂ sensor 660(e.g. a Nondispersive Infrared (NDIR) CO₂ Sensor). Flow sensor 640 may,as here depicted, be an integral part of side-stream CO₂ monitor 610,however other configurations, (e.g. a separate flow sensor) are alsoapplicable and as such within the scope of the present disclosure.

Processor 645 is further configured to determine a duration of time(ΔT_(sl)) for a sample of gas to flow from a reference point 625 in gassampling cannula 650 to side-stream CO₂ monitor 610, to synchronize intime the CO₂ concentration measurement with the flow dynamicsmeasurement, based on the determined ΔT_(sl) and to determine a volumeof exhaled CO₂ as a function of time, based on the obtained flowdynamics measurement and the synchronized CO₂ concentration measurement.

Processor 645 may determine the ΔT_(sl) by providing a bolus of airhaving a known CO₂ concentration and determining the time until a CO₂concentration measurement, corresponding to the known concentration, isobserved. The known CO₂ concentration may include a concentration higherthan a CO₂ concentration potentially observed in exhaled breath, thusleading to a peak in the CO₂ concentration measurement. Alternatively,the known CO₂ concentration may include a concentration lower than a CO₂concentration observed in exhaled breath, thus causing a notch in theCO₂ concentration measurement (and/or the CO₂ waveform derivedtherefrom).

Processor 645 may further determine a shape distortion factor based onthe shape of the notch in the CO₂ waveform and its deviation from ananticipated shape, as described herein. The shape distortion factor maysubsequently be utilized by processor 645 to cancel out distortions tothe shape of the CO₂ waveform caused by friction of the sampling tube'swall on breath sample flow therein, thereby enabling the determining ofthe “true” shape of the obtained CO₂ waveform.

To provide the bolus of clean air, system 600 includes a tube 685through which the bolus of clean air is supplied. Tube 685 is connectedon one side to a position close to gas sampling cannula 650 and on theother side to an air supply 689 configured to supply the bolus of airhaving the known CO₂ concentration.

System 600 further includes a valve 687 positioned in proximity topatient gas sampling cannula 650. Valve 687 may be normally closed,preventing clean air from being pumped in at all times. Valve 687 may beopened for a short period of time and the opening may, for example, becoordinated with the flow dynamics measurements, such that the openingof the valve is triggered by a change in direction from exhalation toinhalation. Additionally or alternatively, operation of valve 687 andhence the injection of the bolus of air having the known CO₂concentration may be defined using algorithms, which, based on learnedcharacteristics as well as measured patient respiration characteristics,enable triggering the injection so as to occur during the plateau of theCO₂ waveform. Additionally or alternatively, valve 687 may induce aplurality of injections ensuring an identifiable notch/peak. Processor645 may then be configured to determine ΔT_(sl) based on the timerequired for the bolus of clean air to be measured by capnograph 610 andto create a notch in the CO₂ waveform, as depicted in FIG. 7.

Reference is now made to FIG. 7, which shows an illustrative a capnogram700, according to some embodiments. Capnogram 700 depicts the CO₂concentration over time in a patient's exhaled breath. Capnogram 700enables calculation of ΔT_(sl) based on an injection of a bolus of cleanair and/or a bolus of air having a known CO₂ concentration into thepatient's breath sample, at a predetermined time point (T_(injection))during the patient's breath cycle. Due to the time for the bolus of airto travel from the reference point (e.g. within the airway adaptor) tothe CO₂ monitor, the notch 710 (or peak) in the CO₂ concentration isonly observed at T_(detection), and the time-lag between T_(injection)and T_(detection) corresponds to ΔT_(sl).

Reference is now made to FIG. 8, which is an illustrative flowchart 800of a method for performing volumetric side-stream capnography, accordingto some embodiments. It is understood that certain steps are sequentialwhereas other steps may be performed either sequentially orsimultaneously with other steps of the method.

At step 810, flow dynamics measurements and CO₂ concentrationmeasurements are obtained. At step 820 an on-start of inhalation (T_(i))is determined based on the flow dynamics measurements. At step 830, theduration of time between T_(i) until the capnograph depicts a deflectionin the CO₂ concentration measurements (ΔT_(TOTAL)) (at the end of theCO₂ waveform) is determined based on an integrated analysis of the flowdynamics measurements and the CO₂ concentration measurements. At step840, a time to wash away a gas volume encompassed between a Y-piece of aventilator and the RP (ΔT_(FLUSH)) is calculated based on theinspiratory flow rate of the ventilator and the gas volume encompassedbetween the Y-piece of the ventilator and the RP. It is understood toone of ordinary skill in the art that ΔT_(FLUSH) may be predeterminedand thus retrieved rather than being calculated as an integral part ofthe method. At step 850, a duration of time (ΔT_(sl)) for a sample ofgas to flow from a reference point to the side-stream CO₂ monitor iscalculated based on the determined ΔT_(FLUSH) and ΔT_(TOTAL). At step860, the CO₂ concentration measurement is synchronized in time with theflow dynamics measurement, based on the determined ΔT_(sl); and in step870, the volume of CO₂ exhaled as a function of time is determined basedon the flow dynamics measurement and the synchronized CO₂ concentrationmeasurement.

Reference is now made to FIG. 9, which is an illustrative flowchart 900of a method for performing volumetric side-stream capnography, accordingto some embodiments. It is understood that certain steps are sequentialwhereas other steps may be performed either sequentially orsimultaneously with other steps of the method.

At step 910, flow dynamics measurements and CO₂ concentrationmeasurements are obtained for at least two different sample flow rates.At step 920 an on-start of inhalation (T_(i)) is determined based on theflow dynamics measurements. At step 930, the duration of time betweenT_(i) until the capnograph depicts a deflection in the CO₂ concentrationmeasurements (ΔT_(TOTAL)) (at the end of the CO₂ waveform) is determinedfor each of the two different sampling flow rates. At step 940, aduration of time (ΔT_(sl)) for a sample of gas to flow from a referencepoint to the side-stream CO₂ monitor is calculated based on thedifference in ΔT_(TOTAL) obtained. At step 950, the CO₂ concentrationmeasurement is synchronized in time with the flow dynamics measurement,based on the determined ΔT_(sl); and in step 960, the volume of CO₂exhaled as a function of time is determined based on the flow dynamicsmeasurement and the synchronized CO₂ concentration measurement.

Reference is now made to FIG. 10, which is an illustrative flowchart1000 of a method for performing volumetric side-stream capnography,according to some embodiments. It is understood that certain steps aresequential whereas other steps may be performed either sequentially orsimultaneously with other steps of the method.

At step 1010, flow dynamics measurements and CO₂ concentrationmeasurements (and or CO₂ waveforms) are obtained. At step 1020 a bolusof clean air and/or a bolus of a gas having a known CO₂ concentration isprovided. The bolus of air may be optionally be provided at initiationof inhalation (T_(i)), as further explained herein. This may be ofparticular importance when the air supplied is clean air from theventilator. At step 1030 the duration of time (ΔT_(sl)) for a sample ofgas to flow from a reference point to the side-stream CO₂ monitor iscalculated based on a time required, until a notch in the CO₂concentration measurements, resulting from the bolus of supplied air, isevident. At step 1040, the CO₂ concentration measurement is synchronizedin time with the flow dynamics measurement, based on the determinedΔT_(sl); and in step 1050, the volume of CO₂ exhaled as a function oftime is determined based on the flow dynamics measurement and thesynchronized CO₂ concentration measurement.

Reference is now made to FIG. 11, which is an illustrative flowchart1100 of a method for determining an undistorted shape of a CO₂ waveform,according to some embodiments. It is understood that certain steps aresequential whereas other steps may be performed either sequentially orsimultaneously with other steps of the method. At step 1110, CO₂concentration measurements are obtained and a CO₂ waveform determinedtherefrom. In step 1120 a bolus of clean air and/or a bolus of a gashaving a known CO₂ concentration is provided, and in 1130 the shape of anotch in the CO₂ waveform resulting from the provided bolus of gas isdetermined. In step 1140, the anticipated shape of the notch isdetermined based on its known volume over time, as described herein. Instep 1150 a shape distortion factor is calculated based on the deviationbetween the obtained shape of the notch and its anticipated shape. Instep 1160, the calculated shape distortion factor is applied on the CO₂waveform, so as to correct for the distortion in its shape, therebyobtaining a CO₂ waveform having an undistorted shape.

Reference is now made to FIG. 12, which is an illustrative flowchart1200 of a method for performing volumetric side-stream capnography,according to some embodiments. It is understood that certain steps aresequential whereas other steps may be performed either sequentially orsimultaneously with other steps of the method.

At step 1210, flow dynamics measurements and CO₂ concentrationmeasurements (and or CO₂ waveforms) are obtained. At step 1220 a bolusof clean air and/or a bolus of a gas having a known CO₂ concentration isprovided. The bolus of air may be provided at initiation of inhalation(T_(i)), as further explained herein. This may be of particularimportance when the air supplied is clean air from the ventilator. Atstep 1230 the duration of time (ΔT_(sl)) required for a sample of gas toflow from a reference point to the side-stream CO₂ monitor is calculatedbased on a time required, until a notch in the CO₂ concentrationmeasurements, resulting from the bolus of supplied air, is evident. Atstep 1240 a shape distortion factor is calculated based on the shape ofthe notch in the CO₂ waveform and, in step 1250 its deviation from ananticipated shape is determined, as described herein. In step 1260, theshape distortion factor may be utilized to cancel out distortions to theshape of the CO₂ waveform caused by friction of the sampling tube's wallon breath sample flow therein, thereby obtaining a correctly shaped CO₂waveform. At step 1270, the CO₂ concentration measurement issynchronized in time with the flow dynamics measurement, based on thedetermined ΔT_(sl); and in step 1280, the volume of CO₂ exhaled as afunction of time is determined based on the flow dynamics measurement,the synchronized CO₂ concentration measurement and the correctly shapedCO₂ waveform.

The techniques may be described in the general context ofcomputer-executable instructions, such as program modules, beingexecuted by a computer. Generally, program modules include routines,programs, objects, components, data structures, and so forth, whichperform particular tasks or implement particular abstract data types.The invention may also be practiced in distributed computingenvironments where tasks are performed by remote processing devices thatare linked through a communications network. In a distributed computingenvironment, program modules may be located in both local and remotecomputer storage media including memory storage devices.

While a number of exemplary aspects and embodiments have been discussedabove, those of skill in the art will recognize certain modifications,additions and sub-combinations thereof. It is therefore intended thatthe following appended claims and claims hereafter introduced beinterpreted to include all such modifications, additions andsub-combinations as are within their true spirit and scope.

The invention claimed is:
 1. A method for determining a volume ofexhaled CO₂ as a function of time using side-stream capnography, themethod comprising: obtaining flow dynamics measurements of a subjectfrom a flow sensor; obtaining CO₂ concentration measurements of asubject from a side-stream CO₂ monitor; determining a duration of time(ΔT_(sl)) for a sample of gas to flow from a reference point to theside-stream CO₂ monitor, wherein determining of the ΔT_(sl) is performedbased on an on-start of inhalation (T_(i)) a duration of time betweenT_(i) until the capnograph depicts a deflection in the CO₂ concentrationmeasurements (ΔT_(TOTAL)) and a time to wash away a gas volumeencompassed between a Y-piece of a ventilator and the reference point RP(ΔT_(FLUSH)), wherein (ΔT_(FLUSH)) is calculated based on theinspiratory flow rate of the ventilator and the gas volume encompassedbetween the Y-piece of the ventilator and the RP synchronizing in timethe CO₂ concentration measurement with the flow dynamics measurement,based on the determined ΔT_(sl); and determining a volume of CO₂ exhaledas a function of time, based on the flow dynamics measurement and thesynchronized CO₂ concentration measurement.
 2. The method of claim 1,wherein the T_(i) is derived from the flow dynamics measurements.
 3. Themethod of claim 1, wherein the ΔT_(sl) is calculated based on adifference in ΔT_(TOTAL) obtained when supplying the volume of air at atleast two different flow rates.
 4. The method of claim 1, wherein T_(i)is determined based on the flow dynamics measurements.
 5. A device fordetermining a volume of exhaled CO₂ as a function of time, the devicecomprising: a side-stream CO₂ monitor configured to measure CO₂concentration over time; and a processor configured to: obtain flowdynamics measurements; obtain the CO₂ concentration measurements fromthe side-stream CO₂ monitor; determine a duration of time (ΔT_(sl)) fora sample of gas to flow from a reference point to the side-stream CO₂monitor, wherein the processor is configured to determine the ΔT_(sl)based on an inspiratory time (ΔT_(in)) and a time to wash away a gasvolume encompassed between a Y-piece of a ventilator and the RP(ΔT_(FLUSH)), wherein (ΔT_(FLUSH)) is calculated based on theinspiratory flow rate of the ventilator and the gas volume encompassedbetween the Y-piece of the ventilator and the RP; synchronize in timethe CO₂ concentration measurement with the flow dynamics measurementbased on the determined ΔT_(sl); and determine a volume of CO₂ exhaledas a function of time based on the flow dynamics measurement and thesynchronized CO₂ concentration measurement.
 6. The device of claim 5,comprising a flow sensor configured to provide flow dynamicsmeasurements.
 7. The device of claim 5, wherein the processor isconfigured to calculate the ΔT_(in) based on a volume of air supplied bythe ventilator and an inspiratory flow rate of the ventilator.
 8. Thedevice of claim 5, wherein the processor is configured to calculate theΔT_(FLUSH) based on a difference in ΔT_(in) obtained when supplying thevolume of air at at least two different flow rates.
 9. The device ofclaim 5, wherein T_(i) is determined based on the flow dynamicsmeasurements.